Dens, C. | Search bioRxiv

bioRxiv2023

The pitfalls of negative data bias for the T-cell epitope specificity challenge

Summary / AbstractEven high-performing machine learning models can have problems when deployed in a real-world setting if the data used to train and test the model contains biases. TCR-epitope binding prediction for novel epitopes is a very important but yet unsolved problem in immunology. In this article, we describe how the technique used to create negative data for the TCR-epitope interaction prediction task can lead to a strong bias and makes that the performance drops to random when tested in a more realistic scenario.

bioinformatics↗

bioRxiv2022

Interpretable deep learning to uncover the molecular binding patterns determining TCR-epitope interactions

The recognition of an epitope by a T-cell receptor (TCR) is crucial for eliminating pathogens and establishing immunological memory. Prediction of the binding of any TCR-epitope pair is still a challenging task, especially for novel epitopes, because the underlying patterns are largely unknown to domain experts and machine learning models. To achieve a deeper understanding of TCR-epitope interactions, we have used interpretable deep learning techniques to gain insights into the performance of TCR-epitope binding machine learning models. We demonstrate how interpretable AI techniques can be linked to the three-dimensional structure of molecules to offer novel insights into the factors that determine TCR affinity on a molecular level. Additionally, our results show the importance of using interpretability techniques to verify the predictions of machine learning models for challenging molecular biology problems where small hard-to-detect problems can accumulate to inaccurate results.

bioinformatics↗